Abstract

We have developed a multifocal optical fluorescence correlation spectroscopy system for parallel flow analyses. Multifocal excitation was made possible through a 4 × 1 diffractive optical fan-out element, which produces uniform intensity in all four foci. Autocorrelation flow analyses inside a 20 µm × 20 µm square microchannel, with the 4 × 1 fan-out foci perpendicular to the flow direction, made it possible to monitor different flows in all four foci simultaneously. We were able to perform cross-correlation flow analyses by turning the microstructure, thereby having all four foci parallel to the direction of flow. Transport effects of the diffusion as a function of flow and distance could then also be studied.

© 2002 Optical Society of America

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    [CrossRef]

2002 (3)

2001 (2)

B. H. Weigl, R. L. Bardell, N. Kesler, C. J. Morris, “Lab-on-a-chip sample preparation using laminar fluid diffusion interfaces—computional fluidic dynamics model results and fluidic verification experiments,” Fresenius J. Anal. Chem. 371, 97–105 (2001).
[CrossRef] [PubMed]

D. S. Mehta, C. Y. Lee, A. Chiou, “Multipoint parallel excitation and CCD-based imaging system for high-throughput fluorescence detection of biochip micro-arrays,” Opt. Commun. 190, 59–68 (2001).
[CrossRef]

2000 (4)

S. A. Zugel, F. E. Lytle, “Two-photon excitation in square and cylindrical capillaries,” Appl. Spectrosc. 54, 1203–1207 (2000).
[CrossRef]

D. J. Lockhart, E. A. Winzeler, “Genomics, gene expression and DNA arrays,” Nature 405, 827–836 (2000).
[CrossRef] [PubMed]

D. R. Walt, “Bead based fiber-optical arrays,” Science 287, 451–452 (2000).
[CrossRef] [PubMed]

M. Gösch, H. Blom, J. Holm, T. Heino, R. Rigler, “Hydrodynamic flow profiling in microstructures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72, 3260–3265 (2000).
[CrossRef]

1999 (3)

M. Brinkmeier, K. Dörre, J. Stephan, M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71, 609–616 (1999).
[CrossRef] [PubMed]

R. J. Lipshutz, S. P. Fodor, T. R. Gingeras, D. J. Lockhart, “High density synthetic oligonucleotide arrays,” Nature Genet. 21, 20–24 (1999).
[CrossRef] [PubMed]

H. Martinsson, J. Bengtsson, M. Ghisoni, A. Larsson, “Monolithic integration of VCSEL and diffractive optical element for advanced beam shaping,” IEEE Photon. Technol. Lett. 11, 503–505 (1999).
[CrossRef]

1998 (4)

D. Whitecomb, C. R. Newton, S. Little, “Advantages in approaches to DNA-based diagnostics,” Curr. Opin. Biotechnol. 9, 602–608 (1998).
[CrossRef]

N. S. Gray, L. Wodicka, A.-M. W. H. Thunnissen, T. C. Norman, S. Kwon, F. H. Espinoza, D. O. Morgan, G. Barnes, S. LeClerc, L. Meijer, S.-H. Kim, D. J. Lockhart, P. G. Schultz, “Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors,” Science 281, 533–538 (1998).
[CrossRef] [PubMed]

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

1997 (2)

M. R. Taghizadeh, P. Blair, B. Layet, I. M. Barton, A. J. Waddie, N. Ross, “Design and fabrication of diffractive optical elements,” Microelectron. Eng. 34, 219–242 (1997).
[CrossRef]

J. Bengtsson, “Design of fan-out kinoforms in the entire scalar diffraction regime with an optimal-rotation-angle method,” Appl. Opt. 36, 8435–8444 (1997).
[CrossRef]

1996 (2)

R. A. Keller, W. P. Ambrose, P. M. Goodwin, J. H. Jett, J. C. Martin, W. Ming, “Single-molecule fluorescence analysis in solution,” Appl. Spectrosc. 50, 12A–32A (1996).
[CrossRef]

L. C. Usich-Wilson, X.-D. Xiang, P. G. Schultz, “Lessons from the immune system: from catalysis to materials science,” Acc. Chem. Res. 29, 164–170 (1996).
[CrossRef]

1995 (3)

M. Schena, D. Shalon, R. W. Davis, P. O. Brown, “Quantitative monitoring of gene expression patterns with a complementary DNA microarray,” Science 270, 467–470 (1995).
[CrossRef] [PubMed]

K. Q. Xia, Y. B. Xin, P. Tong, “Dual-beam incoherent cross-correlation spectroscopy,” J. Opt. Soc. Am. A 12, 1571–1578 (1995).
[CrossRef]

M. Brinkmeier, R. Rigler, “Flow analysis by means of fluorescence correlation spectroscopy,” Exp. Tech. Phys. 41, 205–210 (1995).

1993 (2)

R. Rigler, U. Metz, J. Widengren, P. Kask, “Fluorescence correlation spectroscopy with high count rate and low background: analysis of translational diffusion,” Eur. Biophys. J. 22, 169–175 (1993).
[CrossRef]

S. A. Soper, H. L. Nutter, R. A. Keller, L. M. Davis, E. B. Shera, “The photophysical constants of several fluorescent dyes pertaining to ultra sensitive fluorescence spectroscopy,” Photochem. Photobiol. 57, 972–977 (1993).
[CrossRef]

1978 (1)

M. Magde, W. W. Webb, E. L. Elson, “Fluorescence correlation spectroscopy. III. Uniform translation and laminar flow,” Biopolymers 17, 361–376 (1978).
[CrossRef]

1974 (3)

D. Magde, E. L. Elson, “Fluorescence correlation spectroscopy. I. Conceptual basis and theory,” Biopolymers 13, 1–27 (1974).
[CrossRef]

M. Magde, E. L. Elson, W. W. Webb, “Fluorescence correlation spectroscopy. II. Experimental realizations,” Biopolymers 13, 29–61 (1974).
[CrossRef] [PubMed]

M. Ehrenberg, R. Rigler, “Rotational Brownian motion and fluorescence intensity fluctuations,” Chem. Phys. 4, 390–401 (1974).
[CrossRef]

Ambrose, W. P.

Bardell, R. L.

B. H. Weigl, R. L. Bardell, N. Kesler, C. J. Morris, “Lab-on-a-chip sample preparation using laminar fluid diffusion interfaces—computional fluidic dynamics model results and fluidic verification experiments,” Fresenius J. Anal. Chem. 371, 97–105 (2001).
[CrossRef] [PubMed]

Barnes, G.

N. S. Gray, L. Wodicka, A.-M. W. H. Thunnissen, T. C. Norman, S. Kwon, F. H. Espinoza, D. O. Morgan, G. Barnes, S. LeClerc, L. Meijer, S.-H. Kim, D. J. Lockhart, P. G. Schultz, “Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors,” Science 281, 533–538 (1998).
[CrossRef] [PubMed]

Barton, I. M.

M. R. Taghizadeh, P. Blair, B. Layet, I. M. Barton, A. J. Waddie, N. Ross, “Design and fabrication of diffractive optical elements,” Microelectron. Eng. 34, 219–242 (1997).
[CrossRef]

Bassett, D. E.

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

Bengtsson, J.

Bennett, H. A.

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

Berno, A.

D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

Blair, P.

M. R. Taghizadeh, P. Blair, B. Layet, I. M. Barton, A. J. Waddie, N. Ross, “Design and fabrication of diffractive optical elements,” Microelectron. Eng. 34, 219–242 (1997).
[CrossRef]

Blom, H.

H. Blom, M. Johansson, A.-S. Hedman, L. Lundberg, A. Hanning, S. Hård, R. Rigler, “Parallel fluorescence detection of single biomolecules in microarrays using diffractive optical designed 2 × 2 fan-out element,” Appl. Opt. 41, 3336–3342 (2002).
[CrossRef] [PubMed]

M. Gösch, H. Blom, J. Holm, T. Heino, R. Rigler, “Hydrodynamic flow profiling in microstructures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72, 3260–3265 (2000).
[CrossRef]

Brinkmeier, M.

M. Brinkmeier, K. Dörre, J. Stephan, M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71, 609–616 (1999).
[CrossRef] [PubMed]

M. Brinkmeier, R. Rigler, “Flow analysis by means of fluorescence correlation spectroscopy,” Exp. Tech. Phys. 41, 205–210 (1995).

Brown, P. O.

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

M. Schena, D. Shalon, R. W. Davis, P. O. Brown, “Quantitative monitoring of gene expression patterns with a complementary DNA microarray,” Science 270, 467–470 (1995).
[CrossRef] [PubMed]

Burchard, J.

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

Chee, M.

D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

Chiou, A.

D. S. Mehta, C. Y. Lee, A. Chiou, “Multipoint parallel excitation and CCD-based imaging system for high-throughput fluorescence detection of biochip micro-arrays,” Opt. Commun. 190, 59–68 (2001).
[CrossRef]

Cox, J. A.

J. A. Cox, B. S. Fritz, T. R. Werner, “Process error limitations on binary optics performance,” in Computer and Optically Generated Holographic Optics, 4th in a Series, I. Cindrich, S. H. Lee, eds., Proc. SPIE1555, 80–88 (1991).

Dai, H.

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

Davis, L. M.

S. A. Soper, H. L. Nutter, R. A. Keller, L. M. Davis, E. B. Shera, “The photophysical constants of several fluorescent dyes pertaining to ultra sensitive fluorescence spectroscopy,” Photochem. Photobiol. 57, 972–977 (1993).
[CrossRef]

Davis, R. W.

M. Schena, D. Shalon, R. W. Davis, P. O. Brown, “Quantitative monitoring of gene expression patterns with a complementary DNA microarray,” Science 270, 467–470 (1995).
[CrossRef] [PubMed]

DeRisi, J. L.

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

Dickey, F. M.

S. C. Holswade, F. M. Dickey, “Gaussian laser beam shaping: test and evaluation” in Current Developments in Optical Design and Engineering VI, R. E. Fischer, W. J. Smith, eds., Proc. SPIE2863, 237–245 (1996).

Dörre, K.

M. Brinkmeier, K. Dörre, J. Stephan, M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71, 609–616 (1999).
[CrossRef] [PubMed]

Ehrenberg, M.

M. Ehrenberg, R. Rigler, “Rotational Brownian motion and fluorescence intensity fluctuations,” Chem. Phys. 4, 390–401 (1974).
[CrossRef]

Eigen, M.

M. Brinkmeier, K. Dörre, J. Stephan, M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71, 609–616 (1999).
[CrossRef] [PubMed]

Elson, E. L.

M. Magde, W. W. Webb, E. L. Elson, “Fluorescence correlation spectroscopy. III. Uniform translation and laminar flow,” Biopolymers 17, 361–376 (1978).
[CrossRef]

M. Magde, E. L. Elson, W. W. Webb, “Fluorescence correlation spectroscopy. II. Experimental realizations,” Biopolymers 13, 29–61 (1974).
[CrossRef] [PubMed]

D. Magde, E. L. Elson, “Fluorescence correlation spectroscopy. I. Conceptual basis and theory,” Biopolymers 13, 1–27 (1974).
[CrossRef]

Espinoza, F. H.

N. S. Gray, L. Wodicka, A.-M. W. H. Thunnissen, T. C. Norman, S. Kwon, F. H. Espinoza, D. O. Morgan, G. Barnes, S. LeClerc, L. Meijer, S.-H. Kim, D. J. Lockhart, P. G. Schultz, “Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors,” Science 281, 533–538 (1998).
[CrossRef] [PubMed]

Fang, J.-B.

D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

Fodor, S. P.

R. J. Lipshutz, S. P. Fodor, T. R. Gingeras, D. J. Lockhart, “High density synthetic oligonucleotide arrays,” Nature Genet. 21, 20–24 (1999).
[CrossRef] [PubMed]

Friend, S. H.

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

Fritz, B. S.

J. A. Cox, B. S. Fritz, T. R. Werner, “Process error limitations on binary optics performance,” in Computer and Optically Generated Holographic Optics, 4th in a Series, I. Cindrich, S. H. Lee, eds., Proc. SPIE1555, 80–88 (1991).

Ghandour, G.

D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

Ghisoni, M.

H. Martinsson, J. Bengtsson, M. Ghisoni, A. Larsson, “Monolithic integration of VCSEL and diffractive optical element for advanced beam shaping,” IEEE Photon. Technol. Lett. 11, 503–505 (1999).
[CrossRef]

Gingeras, T. R.

R. J. Lipshutz, S. P. Fodor, T. R. Gingeras, D. J. Lockhart, “High density synthetic oligonucleotide arrays,” Nature Genet. 21, 20–24 (1999).
[CrossRef] [PubMed]

Goodwin, P. M.

Gösch, M.

M. Gösch, H. Blom, J. Holm, T. Heino, R. Rigler, “Hydrodynamic flow profiling in microstructures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72, 3260–3265 (2000).
[CrossRef]

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D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

Stephan, J.

M. Brinkmeier, K. Dörre, J. Stephan, M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71, 609–616 (1999).
[CrossRef] [PubMed]

Stoughton, R.

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

Taghizadeh, M. R.

M. R. Taghizadeh, P. Blair, B. Layet, I. M. Barton, A. J. Waddie, N. Ross, “Design and fabrication of diffractive optical elements,” Microelectron. Eng. 34, 219–242 (1997).
[CrossRef]

Thunnissen, A.-M. W. H.

N. S. Gray, L. Wodicka, A.-M. W. H. Thunnissen, T. C. Norman, S. Kwon, F. H. Espinoza, D. O. Morgan, G. Barnes, S. LeClerc, L. Meijer, S.-H. Kim, D. J. Lockhart, P. G. Schultz, “Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors,” Science 281, 533–538 (1998).
[CrossRef] [PubMed]

Tong, P.

Topaloglou, T.

D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
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L. C. Usich-Wilson, X.-D. Xiang, P. G. Schultz, “Lessons from the immune system: from catalysis to materials science,” Acc. Chem. Res. 29, 164–170 (1996).
[CrossRef]

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D. J. LeCaptain, A. Van Orden, “Two-beam fluorescence cross-correlation spectroscopy in an electrophoretic mobility shift assay,” Anal. Chem. 74, 1171–1176 (2002).
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M. R. Taghizadeh, P. Blair, B. Layet, I. M. Barton, A. J. Waddie, N. Ross, “Design and fabrication of diffractive optical elements,” Microelectron. Eng. 34, 219–242 (1997).
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D. R. Walt, “Bead based fiber-optical arrays,” Science 287, 451–452 (2000).
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D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
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M. Magde, W. W. Webb, E. L. Elson, “Fluorescence correlation spectroscopy. III. Uniform translation and laminar flow,” Biopolymers 17, 361–376 (1978).
[CrossRef]

M. Magde, E. L. Elson, W. W. Webb, “Fluorescence correlation spectroscopy. II. Experimental realizations,” Biopolymers 13, 29–61 (1974).
[CrossRef] [PubMed]

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B. H. Weigl, R. L. Bardell, N. Kesler, C. J. Morris, “Lab-on-a-chip sample preparation using laminar fluid diffusion interfaces—computional fluidic dynamics model results and fluidic verification experiments,” Fresenius J. Anal. Chem. 371, 97–105 (2001).
[CrossRef] [PubMed]

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J. A. Cox, B. S. Fritz, T. R. Werner, “Process error limitations on binary optics performance,” in Computer and Optically Generated Holographic Optics, 4th in a Series, I. Cindrich, S. H. Lee, eds., Proc. SPIE1555, 80–88 (1991).

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D. Whitecomb, C. R. Newton, S. Little, “Advantages in approaches to DNA-based diagnostics,” Curr. Opin. Biotechnol. 9, 602–608 (1998).
[CrossRef]

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R. Rigler, U. Metz, J. Widengren, P. Kask, “Fluorescence correlation spectroscopy with high count rate and low background: analysis of translational diffusion,” Eur. Biophys. J. 22, 169–175 (1993).
[CrossRef]

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D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

Winzeler, E. A.

D. J. Lockhart, E. A. Winzeler, “Genomics, gene expression and DNA arrays,” Nature 405, 827–836 (2000).
[CrossRef] [PubMed]

Wodicka, L.

N. S. Gray, L. Wodicka, A.-M. W. H. Thunnissen, T. C. Norman, S. Kwon, F. H. Espinoza, D. O. Morgan, G. Barnes, S. LeClerc, L. Meijer, S.-H. Kim, D. J. Lockhart, P. G. Schultz, “Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors,” Science 281, 533–538 (1998).
[CrossRef] [PubMed]

Xia, K. Q.

Xiang, X.-D.

L. C. Usich-Wilson, X.-D. Xiang, P. G. Schultz, “Lessons from the immune system: from catalysis to materials science,” Acc. Chem. Res. 29, 164–170 (1996).
[CrossRef]

Xin, Y. B.

Young, P.

D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

Zugel, S. A.

Acc. Chem. Res. (1)

L. C. Usich-Wilson, X.-D. Xiang, P. G. Schultz, “Lessons from the immune system: from catalysis to materials science,” Acc. Chem. Res. 29, 164–170 (1996).
[CrossRef]

Anal. Chem. (3)

M. Brinkmeier, K. Dörre, J. Stephan, M. Eigen, “Two-beam cross-correlation: a method to characterize transport phenomena in micrometer-sized structures,” Anal. Chem. 71, 609–616 (1999).
[CrossRef] [PubMed]

D. J. LeCaptain, A. Van Orden, “Two-beam fluorescence cross-correlation spectroscopy in an electrophoretic mobility shift assay,” Anal. Chem. 74, 1171–1176 (2002).
[CrossRef] [PubMed]

M. Gösch, H. Blom, J. Holm, T. Heino, R. Rigler, “Hydrodynamic flow profiling in microstructures by single molecule fluorescence correlation spectroscopy,” Anal. Chem. 72, 3260–3265 (2000).
[CrossRef]

Appl. Opt. (3)

Appl. Spectrosc. (2)

Biopolymers (3)

D. Magde, E. L. Elson, “Fluorescence correlation spectroscopy. I. Conceptual basis and theory,” Biopolymers 13, 1–27 (1974).
[CrossRef]

M. Magde, E. L. Elson, W. W. Webb, “Fluorescence correlation spectroscopy. II. Experimental realizations,” Biopolymers 13, 29–61 (1974).
[CrossRef] [PubMed]

M. Magde, W. W. Webb, E. L. Elson, “Fluorescence correlation spectroscopy. III. Uniform translation and laminar flow,” Biopolymers 17, 361–376 (1978).
[CrossRef]

Chem. Phys. (1)

M. Ehrenberg, R. Rigler, “Rotational Brownian motion and fluorescence intensity fluctuations,” Chem. Phys. 4, 390–401 (1974).
[CrossRef]

Curr. Opin. Biotechnol. (1)

D. Whitecomb, C. R. Newton, S. Little, “Advantages in approaches to DNA-based diagnostics,” Curr. Opin. Biotechnol. 9, 602–608 (1998).
[CrossRef]

Eur. Biophys. J. (1)

R. Rigler, U. Metz, J. Widengren, P. Kask, “Fluorescence correlation spectroscopy with high count rate and low background: analysis of translational diffusion,” Eur. Biophys. J. 22, 169–175 (1993).
[CrossRef]

Exp. Tech. Phys. (1)

M. Brinkmeier, R. Rigler, “Flow analysis by means of fluorescence correlation spectroscopy,” Exp. Tech. Phys. 41, 205–210 (1995).

Fresenius J. Anal. Chem. (1)

B. H. Weigl, R. L. Bardell, N. Kesler, C. J. Morris, “Lab-on-a-chip sample preparation using laminar fluid diffusion interfaces—computional fluidic dynamics model results and fluidic verification experiments,” Fresenius J. Anal. Chem. 371, 97–105 (2001).
[CrossRef] [PubMed]

IEEE Photon. Technol. Lett. (1)

H. Martinsson, J. Bengtsson, M. Ghisoni, A. Larsson, “Monolithic integration of VCSEL and diffractive optical element for advanced beam shaping,” IEEE Photon. Technol. Lett. 11, 503–505 (1999).
[CrossRef]

J. Opt. Soc. Am. A (1)

Microelectron. Eng. (1)

M. R. Taghizadeh, P. Blair, B. Layet, I. M. Barton, A. J. Waddie, N. Ross, “Design and fabrication of diffractive optical elements,” Microelectron. Eng. 34, 219–242 (1997).
[CrossRef]

Nature (1)

D. J. Lockhart, E. A. Winzeler, “Genomics, gene expression and DNA arrays,” Nature 405, 827–836 (2000).
[CrossRef] [PubMed]

Nature Genet. (1)

R. J. Lipshutz, S. P. Fodor, T. R. Gingeras, D. J. Lockhart, “High density synthetic oligonucleotide arrays,” Nature Genet. 21, 20–24 (1999).
[CrossRef] [PubMed]

Nature Med. (1)

M. J. Marton, J. L. DeRisi, H. A. Bennett, V. R. Iyer, M. R. Meyer, C. J. Roberts, R. Stoughton, J. Burchard, D. Slade, H. Dai, D. E. Bassett, L. H. Hartwell, P. O. Brown, S. H. Friend, “Drug target validation and identification of secondary drug target effects using DNA microarrays,” Nature Med. 4, 1293–1301 (1998).
[CrossRef] [PubMed]

Opt. Commun. (1)

D. S. Mehta, C. Y. Lee, A. Chiou, “Multipoint parallel excitation and CCD-based imaging system for high-throughput fluorescence detection of biochip micro-arrays,” Opt. Commun. 190, 59–68 (2001).
[CrossRef]

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S. A. Soper, H. L. Nutter, R. A. Keller, L. M. Davis, E. B. Shera, “The photophysical constants of several fluorescent dyes pertaining to ultra sensitive fluorescence spectroscopy,” Photochem. Photobiol. 57, 972–977 (1993).
[CrossRef]

Science (4)

M. Schena, D. Shalon, R. W. Davis, P. O. Brown, “Quantitative monitoring of gene expression patterns with a complementary DNA microarray,” Science 270, 467–470 (1995).
[CrossRef] [PubMed]

N. S. Gray, L. Wodicka, A.-M. W. H. Thunnissen, T. C. Norman, S. Kwon, F. H. Espinoza, D. O. Morgan, G. Barnes, S. LeClerc, L. Meijer, S.-H. Kim, D. J. Lockhart, P. G. Schultz, “Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors,” Science 281, 533–538 (1998).
[CrossRef] [PubMed]

D. R. Walt, “Bead based fiber-optical arrays,” Science 287, 451–452 (2000).
[CrossRef] [PubMed]

D. G. Wang, J.-B. Fang, C.-J. Siao, A. Berno, P. Young, R. Sopolsky, G. Ghandour, N. Perkins, E. Winchester, J. Spencer, L. Kruglyak, L. Stein, L. Hsie, T. Topaloglou, E. Hubbel, E. Robinson, M. Mittmann, M. S. Morris, N. Shen, D. Kilburn, J. Rioux, C. Nusbaum, S. Rozen, T. J. Hudson, R. Lipshuts, M. Chee, E. S. Lander, “Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome,” Science 280, 1077–1082 (1998).
[CrossRef] [PubMed]

Other (6)

J. A. Cox, B. S. Fritz, T. R. Werner, “Process error limitations on binary optics performance,” in Computer and Optically Generated Holographic Optics, 4th in a Series, I. Cindrich, S. H. Lee, eds., Proc. SPIE1555, 80–88 (1991).

S. C. Holswade, F. M. Dickey, “Gaussian laser beam shaping: test and evaluation” in Current Developments in Optical Design and Engineering VI, R. E. Fischer, W. J. Smith, eds., Proc. SPIE2863, 237–245 (1996).

R. Rigler, E. S. Elson, eds., Fluorescence Correlation Spectroscopy—Theory and Applications (Springer-Verlag, Berlin, 2001).

A. van den Berg, P. Bergveld, eds., Micro Total Analysis Systems (Kluwer Academic, Dordrecht, The Netherlands, 1994).

D. J. Harrisson, A. van den Berg, eds., Micro Total Analysis Systems ’98 (Kluwer Academic, Dordrecht, The Netherlands, 1998).

A. van den Berg, W. Olthuis, P. Bergveld, eds., Micro Total Analysis Systems 2000 (Kluwer Academic, Dordrecht, The Netherlands, 2000).

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Figures (6)

Fig. 1
Fig. 1

Scanning-electron microscopy pictures showing a 10 µm × 10 µm square microstructure with a superimposed fluorescence pattern from the 4 × 1 diffractive optical fan-out element. The foci in the left-hand pattern numbered 1–4 from top to bottom in the text, and the foci in the right-hand pattern are numbered 1–4 from left to right.

Fig. 2
Fig. 2

Schematic illustration of the setup used for parallel flow measurements in microstructures with a multifocal 4 × 1 diffractive optical designed fan-out element. OD, optical density.

Fig. 3
Fig. 3

Parallel autocorrelation curves of a TMR-4-dUTP solution inside a 20 µm × 20 µm square microchannel. Curves from left to right: focus 4 (solid), focus 3 (stars), focus 2 (crosses), and focus 1 (solid).

Fig. 4
Fig. 4

Parallel flow profiling inside the 20-µm microchannel at several reservoir heights in 5-cm steps from 85 cm (top) to 40 cm (bottom).

Fig. 5
Fig. 5

Cross-correlation curves between foci 1 and 2 inside the 20-µm microchannel, with the reservoir height moved in steps of 5 cm, from 90 cm (left) to 10 cm (right).

Fig. 6
Fig. 6

Cross-correlated flows at a reservoir height of 90 cm. Left to right: foci 1–2, foci 1–3, foci 1–4.

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

gcτ=1+ P1rP2rGr, r, τdrdrC¯2  P1rdr  P2rdr.
P1=P01 exp-2ρ2w02exp-2 z2z02, P2=P02 exp-2ρ-R2w02exp-2 z2z02,
gcτ=1+1N1+ττD1+w02z02ττD1/2-1×exp-1w02Vρτ-R21+τ/τD-1z02Vz2τ21+w02τ/z02τD.
gcτ=1+1N1+ττD1+w02z02ττD1/2-1×exp-Vy2w02τ-τF21+τ/τD.

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